Testicular toxicity produced by ethylene glycol monomethyl and monoethyl ethers in the rat.
Testicular toxicity produced by ethylene glycol monomethyl and monoethyl ethers in the rat.
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乙二醇单甲醚和单乙醚对大鼠产生睾丸毒性。
DOI：
10.1289/ehp.8457207
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发表时间：
1984-08
影响因子：
10.4
通讯作者：
Gray TJ
中科院分区：
文献类型：
--
作者：
Foster PM;Creasy DM;Foster JR;Gray TJ
将乙二醇单甲醚（EGME）和乙二醇单乙醚（EGEE）经口给予年轻雄性大鼠，剂量分别为50至500 mg/kg/天和250至1000 mg/kg/天，持续11天。在连续时间处死动物并检查睾丸组织学。EGME处理后的初始和主要损伤部位仅限于进行偶线期后减数分裂成熟和分裂的初级精母细胞。EGEE产生相同性质的损伤，但需要更大的剂量才能引起相同的严重程度（500 mg EGEE/kg约等于100 mg EGME/kg）。此外，在精母细胞群体中，根据减数分裂成熟的精确阶段观察到不同的敏感性：分裂（阶段XIV）和粗线期早期（阶段I-II）大于粗线期晚期（阶段VIII-XIII）大于粗线期中期（阶段III-VII）。等剂量的甲氧基乙酸（MAA）和乙氧基乙酸（EAA）的损伤与相应的乙二醇醚相似。当动物预处理酒精代谢抑制剂，然后睾丸毒性剂量的EGME（500毫克/公斤），乙醇脱氢酶抑制剂（吡唑）提供了完全的保护。用醛脱氢酶抑制剂双硫仑或帕吉林预处理并没有改善EGME的睾丸毒性。在支持生殖细胞的混合培养物中，MAA而不是EGME对精母细胞产生的影响与体内观察到的类似，浓度约等于单次口服EGME（500 mg/kg）后的稳态血浆水平。似乎可能是代谢产物（MAA或可能是甲氧基乙醛）而不是EGME导致睾丸损伤。
Ethylene glycol monomethyl ether (EGME) and ethylene glycol monoethyl ether (EGEE) were administered orally to young male rats at doses varying from 50 to 500 mg/kg/day and 250 to 1000 mg/kg/day for EGME and EGEE, respectively, for 11 days. At sequential times animals were killed and testicular histology examined. The initial and major site of damage following EGME treatment was restricted to the primary spermatocytes undergoing postzygotene meiotic maturation and division. EGEE produced damage of an identical nature, but a larger dose was required to elicit equivalent severity (500 mg EGEE/kg being approximately equivalent to 100 mg EGME/kg). Additionally, within the spermatocyte population, differential sensitivity was observed depending on the precise stage of meiotic maturation: dividing (stage XIV) and early pachytene (stages I-II) greater than late pachytene (stages VIII-XIII) greater than mid-pachytene (stages III-VII). Equivalent doses of methoxyacetic acid (MAA) and ethoxyacetic acid (EAA) gave injury similar to the corresponding glycol ether. When animals were pretreated with inhibitors of alcohol metabolism followed by a testicular toxic dose of EGME (500 mg/kg), an inhibitor of alcohol dehydrogenase (pyrazole) offered complete protection. Pretreatment with the aldehyde dehydrogenase inhibitors disulfiram or pargyline did not ameliorate the testicular toxicity of EGME. In mixed cultures of Sertoli-germ cells, MAA and not EGME produced effects on spermatocytes analogous to that seen in vivo, at concentrations approximately equivalent to steady-state plasma levels after a single oral dose of EGME (500 mg/kg). It would seem likely that a metabolite (MAA or possibly methoxyacetaldehyde) and not EGME is responsible for the production of testicular damage.